Bioequivalence and Bioavailability Forum

Hi Hötzi,

❝ Given the strange responses I have seen in the recent past from European regulators even on straightforward two-stage designs I would not recommend such an approach – unless a framework is published. Nevertheless, a tempting idea which deserves some attention, IMHO.

❝ ( ElMaestro?)

Si Señor... I'll be happy to write some software which does the EMA thing. But I am short of time at the moment. I am more of a sailor than a simulant these days. Longish WHO trip to the far east coming up as well as a few conferences and blah blah blah.

Simplest case would be to take Potvin's meffuds B and C and to just implement a kinda "pick one" decision at stage 1. The criteria for picking the right one after stage 1 might be based on the PE. But of course it would be subject to debate if apparent variability should also be somehow considered. We could -and this is just a stray thought- do a power calc after stage 1 using the observed PE and then define the winner as the one that is associated with the highest power at this stage. We could of course also just apply the expected PE and it would boil down to lowest Variance wins. Not sure, haven't thought it through at all. And we will need to consider two type I errors, of course.
Oh wait, we also need to consider "chance of one product passing BE criteria", so I guess we'll have three T1Es. Darn... this quickly gets complicated.


Lemme hear some creative thoughts or alternatives. I don't think this is very difficult but it will take a bloody lot of time.